tbuckley/cabot-search huggingface dataset:
Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B
Authors: Martina Musella, Andrea Guarracino, Nicoletta Manduca, Claudia Galassi, Eliana Ruggiero, Alessia Potenza, Ester Maccafeo, Gwenola Manic, Luca Mattiello, Sara Soliman Abdel Rehim, Michele Signore, Marco Pietrosanto, Manuela Helmer-Citterich, Matteo Pallocca, Maurizio Fanciulli, Tiziana Bruno, Francesca De Nicola, Giacomo Corleone, Anna Di Benedetto, Cristiana Ercolani, Edoardo Pescarmona, Laura Pizzuti, Francesco Guidi, Francesca Sperati, Sara Vitale, Daniele Macchia, Massimo Spada, Giovanna Schiavoni, Fabrizio Mattei, Adele De Ninno, Luca Businaro, Valeria Lucarini, Laura Bracci, Eleonora Aricò, Giovanna Ziccheddu, Francesco Facchiano, Stefania Rossi, Massimo Sanchez, Alessandra Boe, Mauro Biffoni, Ruggero De Maria, Ilio Vitale, Antonella Sistigu
Journal: Nature Immunology (2022)

Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I → KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.
PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c‐Myc‐mediated positive feedback loop
Authors: Xinyuan Zhao, Dalong Shu, Wenjuan Sun, Shanshan Si, Wei Ran, Bing Guo, Li Cui
Journal: Cancer Communications (2022)

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis, high lymph node metastasis and early recurrence. However, the molecular events regulating HNSCC tumorigenesis remain poorly understood. Therefore, uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC. In this study, we aimed to explore the role of pleckstrin‐2 (PLEK2) in regulating HNSCC tumorigenesis. Methods The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort. In vitro and in vivo experiments, including cell proliferation, colony formation, Matrigel invasion, tumor sphere formation, ALDEFLUOR, Western blotting assays and xenograft mouse models, were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells. The underlying molecular mechanisms for the tumor‐promoting role of PLEK2 were elucidated using co‐immunoprecipitation, cycloheximide chase analysis, ubiquitination assays, chromatin immunoprecipitation‐quantitative polymerase chain reaction, luciferase reporter assays and rescue experiments. Results The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues, and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance. Additionally, PLEK2 was important for maintaining the proliferation, invasion, epithelial‐mesenchymal transition, cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells. Mechanistically, PLEK2 interacted with c‐Myc and reduced the association of F‐box and WD repeat domain containing 7 (FBXW7) with c‐Myc, thereby avoiding ubiquitination and subsequent proteasome‐mediated degradation of c‐Myc. Moreover, the c‐Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells. c‐Myc also directly bounded to the PLEK2 promoter and activated its transcription, forming a positive feedback loop. Conclusions Collectively, these findings uncover a previously unknown molecular basis of PLEK2‐enhanced c‐Myc signaling in HNSCC, suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.
Proton therapy for adult craniopharyngioma: Experience of a single institution in 91 consecutive patients
Authors: Arnaud Beddok, Nathaniel Scher, Claire Alapetite, Bertrand Baussart, Ghita Bentahila, Franck Bielle, Stephanie Bolle, Remi Dendale, Sylvain Dureau, Farid Goudjl, Sylvie Helfre, Hamid Mammar, Lucia Nichelli, Valentin Calugaru, Loïc Feuvret
Journal: Neuro-Oncology (2022)

Craniopharyngioma (CP) in adults is a rare benign tumor associated with many morbidities, with limited contemporary studies to define treatment, and follow-up guidelines.A single-center retrospective study was conducted on patients aged ≥ 18 years from 2006-2018 with CP and who were treated with proton therapy (PT). Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS), local recurrence-free survival (LRFS), and toxicity were characterized using Kaplan-Meier and Cox regression analyses.Ninety-one patients met the criteria, with a median age of 37 years (range 18-82 years). PT was conducted after tumor resection in 88 patients (97%), in 64 patients (70.3%) as an adjuvant strategy and in 27 (29.7%) after recurrent disease. Three patients received exclusive PT. A median MRI follow-up of 39 months revealed 35.2% complete response, 49.5% partial response, and 9.9% stable disease. Five patients developed local recurrence (LR). The pattern of failure study showed that these five LR were within the GTV volume. The 5-year LRFS was 92.0% [CI 95% 84.90-99.60]. All the patients were alive at the end of the follow-up. Patients requiring treatment adaptation during PT tend to have a higher risk of LR (P = .084). Endocrinopathy was the most frequent grade ≥ 2 late toxicity. Among patients who were symptom-free before the start of treatment, none developed hearing toxicity but four (9.8%) developed visual disorders and 10 (11.3%) symptomatic memory impairment. Patients with large tumors had a higher risk of developing symptomatic memory impairment (P = .029).Adults with CP treated with PT have favorable survival outcomes, with acceptable late toxicity. Prospective quality-of-life and neurocognitive studies are needed to define late adverse effects better.
MicroRNA–Disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice
Authors: Yicong Shen, Yuanxu Gao, Jiangcheng Shi, Zhou Huang, Rongbo Dai, Yi Fu, Yuan Zhou, Wei Kong, Qinghua Cui
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta and is highly lethal. The main purpose of the current study is to search for noninvasive medical therapies for AAA, for which there is currently no effective drug therapy. Network medicine represents a cutting-edge technology, as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective. Here, we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases. Analysis revealed some patterns for these diseases. For instance, diseases tended to be clustered and coherent in the network. Surprisingly, we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus, both of which are autoimmune diseases, suggesting that AAA could be one type of autoimmune diseases in etiology. Based on this observation, we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA. Finally, animal experiments confirmed that methotrexate, a drug for autoimmune diseases, was able to alleviate the formation and development of AAA.
Short- and long-term outcomes of robotic- versus laparoscopic-assisted right hemicolectomy: A propensity score-matched retrospective cohort study
Authors: Yaqi Zhang, Haoran Feng, Shaodong Wang, Yifei Gu, Yi Shi, Zijia Song, Yang Deng, Xiaopin Ji, Xi Cheng, Tao Zhang, Ren Zhao
Journal: International Journal of Surgery (2022)
Histological tumor micronecrosis in resected specimens after R0 hepatectomy for hepatocellular carcinomas is a factor in determining adjuvant TACE: A retrospective propensity score-matched study
Authors: Yangyang Wang, Hongbin Ge, Manyi Hu, Changrong Pan, Mao Ye, Dipesh Kumar Yadav, Rujia Zheng, Jiajun Wu, Ke Sun, Meng Wang, Yu Tian, Jinyan Huang, Weiyun Yao, Jingsong Li, Qi Zhang, Tingbo Liang
Journal: International Journal of Surgery (2022)
CLINICAL HISTORY OF THE CASE OF PRESIDENT JAMES ABRAM GARFIELD.
Authors: ROBERT REYBURN
Journal: JAMA (1894)

(<i>Continued from page 582</i>). The President was more restless than usual last night being evidently excited by the anticipation of the journey. This morning at 5:30 A.M. his temperature was 99.8; pulse 118; respirations 18. September 6 at 6 A.M. the President was tenderly lifted by the devoted friends, who had nursed him through his long and weary illness, and in company with his physicians, he was carried on a stretcher to the outer vestibule of the White House. Twice while being carried he waved his hand in recognition to those of his household he was leaving behind. The bed he had just left had preceded him. He was immediately placed upon it without the least apparent discomfort. The President seemingly enjoyed the proceedings until the car was reached. The hour was fortunately too early for any great congregation of people, yet many who had heard of his intended removal
Biologic pathways for chronic spontaneous urticaria and their regulation by benralizumab
Authors: Debajyoti Ghosh, Rashid Karim, Xiang Zhang, Umesh Singh, Jonathan A. Bernstein
Journal: Allergy (2022)

Appendix S1 Figure S1 Figure S2 Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies
Authors: Sanne de Wit, Claire Glen, Rudolf A de Boer, Ninian N Lang
Journal: Cardiovascular Research (2022)

Heart failure (HF) and cancer are the leading causes of death worldwide and accumulating evidence demonstrates that HF and cancer affect one another in a bidirectional way. Patients with HF are at increased risk for developing cancer, and HF is associated with accelerated tumour growth. The presence of malignancy may induce systemic metabolic, inflammatory, and microbial alterations resulting in impaired cardiac function. In addition to pathophysiologic mechanisms that are shared between cancer and HF, overlaps also exist between pathways required for normal cardiac physiology and for tumour growth. Therefore, these overlaps may also explain the increased risk for cardiotoxicity and HF as a result of targeted anti-cancer therapies. This review provides an overview of mechanisms involved in the bidirectional connection between HF and cancer, specifically focusing upon current 'hot-topics' in these shared mechanisms. It subsequently describes targeted anti-cancer therapies with cardiotoxic potential as a result of overlap between their anti-cancer targets and pathways required for normal cardiac function.
Epidemiology of SARS-CoV-2 infection among staff and students in a cohort of English primary and secondary schools during 2020–2021
Authors: James R. Hargreaves, Sinéad M. Langan, William E. Oswald, Katherine E. Halliday, Joanna Sturgess, Jody Phelan, Patrick Nguipdop-Djomo, Benjamin Ford, Elizabeth Allen, Neisha Sundaram, Georgina Ireland, John Poh, Samreen Ijaz, Ian Diamond, Emma Rourke, Fiona Dawe, Alison Judd, Charlotte Warren-Gash, Taane G. Clark, Judith R. Glynn, W. John Edmunds, Chris Bonell, Punam Mangtani, Shamez N. Ladhani, Tanya Abramsky, Shazaad Ahmad, Felicity Aiano, Frances Baawuah, Urszula Bankiewicz, Sarah Batt, Joanne Beckmann, Ami Bhavsar, Bernadette Brent, Andrew Brent, Simon Brouwer, Kevin Brown, Richard Browne, Kevin Childs, Sarah Cook, Simon Cousens, Ieuan Day, Antonio Felton, Paul Fine, David Foster, Joanna Garstang, David Gates, Claire Grant, Bethany Griffiths-Tong, Claire Hele, Rowan Hemsi, Pete Jones, Helena Jordan, Adam Kucharski, Andrea Lacey, Rebecca Leeson, Ffion Lelii, Philip Lovely, Madeleine Lunskey, Chris McLanachan, James Munday, Ifeanyichukwu Okike, Kathleen O'Reilly, Penelope Parker, Annabel Powell, Sarah Proud, Mary Ramsay, Lee Rudd, Timothy Russell, Justin Shute, Nerissa Tilouche, Charmaine Virgin, Sian-Elin Wyatt, KELLY YEO
Journal: The Lancet Regional Health - Europe (2022)

There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020–July 2021). 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. UK Department of Health and Social Care.
Campaign against Rheumatism
Journal: BMJ (1940)

P.-S.Hench calls attention to the vastness of the problem in America and this country and the neces- sity for more support, both from the Governments and from the public if this scourge is to be tackled adequately." In every country the same findings have been made: (1) rheumatic diseases outrank all others as a cause of chronic morbidity; (2) rheumatic disease annually involves each country in great expense; (3) adequate facilities for the care of most rheumatic patients are non-existent."Hench quotes staggering figures for the United States and compares their prospects with those of others, " for example for 680,000 tuberculous patients there are available about 100,000 free beds and 100,000,000 dollars annually for care and research but for 6,850,000 rheumatic patients there are available only about 200 free beds and 20(,000 dollars annually for care and research.In other words, although there are ten times as many rheumatic as tuberculous patients, the latter have available 500 times more beds and money.Thus the tuberculous patient, happily thereby a vanishing race, receives 5,000 times as much attention as the non-vanishing rheumatic."He points out that a survey of voluntary health agencies in America discloses the astonishing paradox that " the greater the need the less the public support" but considers that this is due simply to the fact that the public has not been sufficiently informed or aroused (sae Table ).
Australia Antigen and Hepatitis
Authors: Baruch S. Blumberg
Journal: JAMA (1969)

In 1965, we reported a "new" antigen, Australia antigen, in the serum of patients with leukemia.<sup>1</sup>Research since then has dealt with the epidemiology, genetics, and physical and chemical characteristics of the antigen,<sup>2</sup>Early in the investigation<sup>3</sup>it became clear that Australia antigen is closely associated with, or may itself be, a causal agent of viral hepatitis.<sup>26</sup>It is estimated that tens of millions of asymptomatic people carry the antigen chronically.<sup>1,2</sup>These deductions have resulted from a systematic study of antigens in human blood with use of sera from multiply transfused patients as sources of antibody. In 1961 Allison and Blumberg hypothesized that individuals receiving multiple transfusions would receive some serum proteins of a phenotype different from their own and would respond by producing antibodies. It was appreciated that both inherited and acquired antigens might occur in human serum and cause antibody formation in blood
Glioma Formation in Neurofibromatosis 1 Reflects Preferential Activation of K-RAS in Astrocytes
Authors: Biplab Dasgupta, Wen Li, Arie Perry, David H. Gutmann
Journal: Cancer Research (2005)

Abstract Children with the tumor predisposition syndrome, neurofibromatosis 1 (NF1), develop optic pathway gliomas. The NF1 gene product, neurofibromin, functions as a negative regulator of RAS, such that NF1 inactivation results in RAS hyperactivation. Recent studies have highlighted the divergent biological and biochemical properties of the various RAS isoforms, which prompted us to examine the consequence of Nf1 inactivation in astrocytes on RAS isoform activation in vitro and in vivo. In this report, we show that only K-RAS is activated in Nf1−/− astrocytes and that activation of K-RAS, but not H-RAS, accounts for the proliferative advantage and abnormal actin cytoskeleton–mediated processes observed in Nf1−/− astrocytes in vitro. Moreover, dominant inhibitory K-RAS corrects these abnormalities in Nf1−/− astrocytes invitro. Lastly, we show that Nf1+/− mice with astrocyte-specific activated K-RAS expression in vivo develop optic pathway gliomas, similar to our previously reported Nf1+/− mice with astrocyte Nf1 inactivation. Collectively, our results show that K-RAS is the primary target for neurofibromin GTPase-activating protein activity in vitro and in vivo and that K-RAS activation in astrocytes recapitulates the biochemical, biological, and tumorigenic properties of neurofibromin loss.
Expression Analysis of Juvenile Pilocytic Astrocytomas by Oligonucleotide Microarray Reveals Two Potential Subgroups
Authors: Kwong-Kwok Wong, Yi-Mieng Chang, Yvonne T.M. Tsang, Laszlo Perlaky, Jack Su, Adekunle Adesina, Dawna L. Armstrong, Meenakshi Bhattacharjee, Robert Dauser, Susan M. Blaney, Murali Chintagumpala, Ching C. Lau
Journal: Cancer Research (2005)

Abstract Juvenile pilocytic astrocytoma (JPA) is one of the most common brain tumors in children. The expression profiles of 21 JPAs, determined using Affymetrix GeneChip U133A, were compared with subjects with normal cerebella. The genes involved in neurogenesis, cell adhesion, synaptic transmission, central nervous system development, potassium ion transport, protein dephosphorylation, and cell differentiation were found to be significantly deregulated in JPA. These 21 JPAs were further clustered into two major groups by unsupervised hierarchical clustering using a set of 848 genes with high covariance (0.5-10). Supervised analysis with Significance Analysis of Microarrays software between these two potential subgroups identified a list of significant differentially expressed genes involved in cell adhesion, regulation of cell growth, cell motility, nerve ensheathment, and angiogenesis. Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein–positively stained tumor cells may have a higher tendency to progress.
Functional Evaluation and Cancer Risk Assessment of BRCA2 Unclassified Variants
Authors: Kangjian Wu, Shannon R. Hinson, Akihiro Ohashi, Daniel Farrugia, Patricia Wendt, Sean V. Tavtigian, Amie Deffenbaugh, David Goldgar, Fergus J. Couch
Journal: Cancer Research (2005)

Abstract The influence of germ line BRCA2 unclassified variants (UCV), including missense mutations and in-frame deletions and insertions on BRCA2 function and on cancer risk, has not been defined although these mutations account for 43% of all identified BRCA2 sequence alterations. To investigate the effects of UCVs on BRCA2 function, we compared mutant and wild-type forms of BRCA2 using assays of cellular survival and viability, homologous recombination repair, and genome instability. We confirm that the effects of known deleterious mutations can be distinguished from neutral polymorphisms and wild-type BRCA2 in these assays, and we characterize the influence of a series of UCVs on BRCA2 function. We also describe how the results from the assays can be combined with data from analysis of cosegregation of the UCVs with cancer, co-occurrence of the UCVs with other deleterious mutations, and interspecies sequence variation in a comprehensive framework in an effort to better distinguish between disease predisposing and neutral UCVs. This combined approach represents a useful means of addressing the functional significance and cancer relevance of UCVs in BRCA2.